Daily vitality fluctuations in older adults with depressive symptoms: A multilevel location-scale model.

BACKGROUND: Examining the daily experiences of older adults with depression facilitates the development and application of personalized effective treatments for them. In previous clinical research on depression, traditional mean-based approaches have mainly been employed. However, the within-person residual variance as a random effect provides greater insight into the heterogeneity of daily experiences among geriatric samples. OBJECTIVE: This study aimed to examine the relationship between depression and daily vitality in older adults. Specifically, it focused on the mean and residual variance of daily vitality measured by the Ecological Momentary Assessment (EMA). METHODS: Data from 64 older adults aged 65 years or more, who participated in community welfare centers or retirees' associations, were used. Daily vitality was examined using EMA surveys for seven consecutive days (four random surveys per day). The data were analyzed using a location-scale model. RESULTS: The intraclass correlation computed from the empty model for the EMA data was 0.488, indicating significant variances in daily vitality across time between individuals. Older adults with higher levels of depressive symptoms showed low mean levels of daily vitality and a large log-residual variance of daily vitality. CONCLUSIONS: The findings from the current study suggest that individuals experiencing depression not only exhibit low vitality in their daily lives but also struggle to maintain stable levels of vitality in their lives. These insights could contribute to the facilitation and advancement of personalized interventions tailored for older adults.

Improving older adults' autobiographical memory through video-conferencing intervention during COVID-19.

BACKGROUND: Autobiographical memory (AM) is valuable not only as an indicator of mental health and cognitive function, but also as a target of therapeutic intervention for older adults. In the context of the COVID-19 pandemic, the demand for online psychosocial interventions and assessment services has sharply increased. Thus, the present study examined the effectiveness of videoconferencing AM (vAM) intervention using the Ecological Momentary Assessment (EMA) method in addition to the traditional paper-and-pencil assessment among samples of community dwelling older adults. METHODS: Twenty-seven older adults (aged 66-86 years) participated in a vAM intervention composed of 4 weekly 90-min sessions. The primary outcome was AM specificity, with secondary outcomes as depressive symptom and cognitive function, measured before and after the intervention. In addition, daily emotions were measured through EMA over 4 weeks of intervention. The EMA data were analyzed using a multilevel analysis. RESULTS: The results showed low dropout rates (7%) and high EMA response rates (85%). Autobiographical memory specificity increased (Cohen's d = 0.678), and the level of depression declined significantly (Cohen's d = 0.375) after the program. Additionally, measures assessing cognitive function, such as Seoul Verbal Learning Test and DSC (Digit Symbol Coding), showed significant improvements. The EMA results indicated a decrease in the intensity and proportion of negative emotions experienced during the program. CONCLUSIONS: This study is the first to utilize videoconferencing and EMA to deliver an AM intervention targeting older adults. The intervention was effective in improving mental health and cognitive function, including AM in older adults. Additionally, EMA was found to be a feasible tool for use in older adults.

Effects of the loss of mismatch repair genes on single-strand annealing between divergent sequences in Saccharomyces cerevisiae.

Eukaryotic genomes contain many duplicated genes closely located with each other, such as the hexose transporter (HXT) genes in Saccharomyces cerevisiae. They can potentially recombine via single-strand annealing (SSA) pathway. SSA between highly divergent sequences generates heteroduplex DNA intermediates with many mismatches, which can be corrected by mismatch repair (MMR), resulting in recombinant sequences with a single junction point. In this report, we demonstrate that SSA between HXT1 and HXT4 genes in MMR-deficient yeast cells produces recombinant genes with multiple-junctions resulting from alternating HXT1 and HXT4 tracts. The mutations in MMR genes had differential effects on SSA frequencies; msh6Δ mutation significantly stimulated SSA events, whereas msh2Δ and msh3Δ slightly suppressed it. We set up an assay that can identify a pair of recombinant genes derived from a single heteroduplex DNA. As a result, the recombinant genes with multiple-junctions were found to accompany genes with single-junctions. Based on the results presented here, a model was proposed to generate multiple-junctions in SSA pathway involving an alternative short-patch repair system.

Analyses of DNA double-strand break repair pathways in tandem arrays of HXT genes of Saccharomyces cerevisiae.

Eukaryotic genomes contain numerous homologous repeat sequences including redundant genes with divergent homology that can be potential recombination targets. Recombination between divergent sequences is rare but poses a substantial threat to genome stability. The hexose transporter (HXT) gene family shares high sequence similarities at both protein and DNA levels, and some members are placed close together in tandem arrays. In this study, we show that spontaneous interstitial deletions occur at significantly high rates in HXT gene clusters, resulting in chimeric HXT sequences that contain a single junction point. We also observed that DNA double-strand breaks created between HXT genes produce primarily interstitial deletions, whereas internal cleavage of the HXT gene resulted in gene conversions as well as deletion products. Interestingly, interstitial deletions were less constrained by sequence divergence than gene conversion. Moreover, recombination-defective mutations differentially affected the survival frequency. Mutations that impair single-strand annealing (SSA) pathway greatly reduced the survival frequency by 10-1,000-fold, whereas disruption of Rad51-dependent homologous recombination exhibited only modest reduction. Our results indicate that recombination in the tandemly repeated HXT genes occurs primarily via SSA pathway.

Strategy for performing treponemal tests in reverse-sequence algorithms of syphilis diagnosis.

OBJECTIVES: In South Korea, automated T. pallidum Latex Agglutination (TPLA) based on turbidoimmunoassays and immunochromatographic assay (ICA) are widely used for syphilis diagnosis. However, there is sparse data on the validation of these assays in the reverse-sequence algorithm setting. METHODS: We assessed 551 specimens submitted for syphilis testing. We compared varying reverse-sequence algorithms using combinations of the Cobas Syphilis EIA (Roche Diagnostics, Mannheim, Germany), Mediace TPLA (Sekisui Medical Co., Tokyo, Japan), TPPA (Fujirebio Inc., Tokyo, Japan), and SD Bioline ICA (Standard Diagnostic, Yongin, Korea). We also evaluated modified algorithms incorporating a cut off of high specificity for EIA and TPLA using receiver operating characteristic curves. RESULTS: The agreement was almost perfect between EIA and TPLA (Kappa, 0.953) and strong between TPPA and ICA (Kappa, 0.887). Among TPPA positive and ICA negative specimens, 67% of the specimens were from individuals with syphilis histories. Compared to EIA/RPR/TPPA, the agreement with EIA/RPR/ICA, TPLA/RPR/TPPA and TPLA/RPR/ICA were almost perfect (Kappa, 0.930, 0.995 and 0.914, respectively). When a cut off of 95% specificity was applied, the number of TPPA tests could be reduced by 44% and 40% in EIA and TPLA, respectively. CONCLUSIONS: TPLA showed almost perfect agreement with EIA and that it could be used in the site of EIA in a reverse sequence algorithm. ICA showed a lower detection rate than TPPA as a 2nd treponemal test and should be used with caution. With cut offs of higher specificity, more efficient reverse-sequence algorithms can be made possible.

Relationship of Circulating Fetuin-A Levels with Body Size and Metabolic Phenotypes.

BACKGROUND: Previous studies have suggested the existence of distinct body size subgroups according to metabolic health referred to as metabolically healthy obesity (MHO) and metabolically abnormal but normal weight (MANW) patients. Although nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and metabolic syndrome, the relationship between these phenotypes and fetuin-A, a representative hepatokine, has not been explored. METHODS: We examined the association between circulating fetuin-A levels, metabolic health phenotypes, cardiometabolic risk parameters, and subclinical atherosclerosis in 290 subjects who were randomly selected from an ongoing cohort study. RESULTS: Fetuin-A concentrations were significantly associated with detrimental anthropometric and laboratory measurements, including increased waist circumference, blood pressure, alanine aminotransferase, fasting plasma glucose, and triglyceride levels. Furthermore, fetuin-A levels were significantly increased in the metabolically abnormal (MA) group compared to the metabolically healthy (MH) group in subjects without obesity (717.1 [632.1, 769.7] vs. 599.5 [502.0, 709.3], P = 0.001) and subjects with obesity (704.1 [595.5-880.9] vs. 612.2 [547.9-802.1], P = 0.016). In addition, brachial-ankle pulse wave velocity (baPWV), which reflects arterial stiffness, was higher in MA individuals compared to MH individuals. Multiple logistic regression analysis revealed that both individuals without obesity (P for trend = 0.017) and with obesity (P for trend = 0.028) in the higher tertiles of fetuin-A had an increased risk of MA than those in the lowest tertile. CONCLUSIONS: This study demonstrates that fetuin-A levels are significantly associated with metabolic health phenotypes, such as MHO and MANW, in Korean adults.

Association of leukocyte cell-derived chemotaxin 2 (LECT2) with NAFLD, metabolic syndrome, and atherosclerosis.

OBJECTIVE: Previous studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a recently discovered hepatokine, is associated with the inflammatory response and insulin resistance. We examined circulating plasma LECT2 levels in the subjects with non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome. METHODS: We analyzed plasma LECT2 levels from the subjects of age- and sex-matched 320 adults with or without NAFLD who completed a health check-up at the Health Promotion Center of Korea University Guro Hospital. RESULTS: Individuals with NAFLD showed significantly higher LECT2 levels (31.2 [20.9, 41.5] vs. 24.5[16.3, 32.7] ng/ml, P <0.001) as well as components of MetS compared to those without NAFLD. Furthermore, circulating LECT2 concentrations were greater in subjects with MetS (32.6 [17.8, 45.0] vs. 27.0 [18.7, 33.7] ng/ml, P = 0.016) and were associated with anthropometric measures of obesity, lipid profiles, high sensitivity C-reactive protein (hsCRP) and liver aminotransferase levels. However, there was no significant relationship between LECT2 levels and indicators of subclinical atherosclerosis, such as carotid intima-media thickness (CIMT) and brachial ankle pulse wave velocity (baPWV). Multivariate analysis demonstrated a progressively increasing trend of odds ratios for NAFLD according to quartiles of LECT2 levels after adjusting for risk factors, although the relationship was attenuated after further adjustment for waist circumference and lipid levels. CONCLUSION: Circulating LECT2 concentrations were increased in individuals with NAFLD and those with MetS, but not in those with atherosclerosis. The relationship between LECT2 and both NAFLD and MetS might be mediated by its association with abdominal obesity and lipid metabolism. TRIAL REGISTRATION: Clinicaltrials.gov NCT01594710.

Knockdown of sestrin2 increases pro-inflammatory reactions and ER stress in the endothelium via an AMPK dependent mechanism.

BACKGROUND & OBJECTIVE: Sestrin2 (sesn2) has recently gained attention as an important regulator for various metabolic disorders. Sesn2 is involved in AMP-activated protein kinase (AMPK) activation, which leads to anti-inflammatory and anti-oxidative responses. However, the role of sesn2 in the endothelium has not yet been clarified. METHODS: To evaluate sesn2-mediated anti-atherosclerotic effects, siRNA to silence sesn2 expression was introduced to human umbilical vein endothelial cells (HUVECs), THP-1 cells and C57BL/6 mice. Lipopolysaccharide (LPS) was administrated to sesn2-knockdown cells and mice to induce atherosclerotic signals. RESULTS: Knockdown of sesn2 was involved with atherosclerotic reactions caused by LPS treatment through decrease of AMPK phosphorylation. In sesn2-knockdown HUVECs and THP-1 cells, LPS-mediated nuclear factor kappa B (NF-κB) phosphorylation and secretion of pro-inflammatory cytokines were both significantly increased. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly increased after sesn2-knockdown. Furthermore, LPS-induced reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and cell toxicity were all significantly elevated after sesn2-knockdown in HUVECs. Interestingly, all these pro-atherosclerotic effects were fully abrogated by treatment with an AMPK activator. In aortic tissue samples from C57BL/6 mice, sesn2-knockdown using siRNA oligomers resulted in reduced AMPK phosphorylation and induction of LPS-mediated NF-κB phosphorylation, leading to up-regulation of adhesion molecules and ER stress-related signaling. CONCLUSION: Knockdown of sesn2 aggravates atherosclerotic processes by increasing pro-inflammatory reactions and ER stress in the endothelium via an AMPK-dependent mechanism, suggesting that sesn2 might be a novel therapeutic target for atherosclerosis.

Tuning the Reactivity of Ultrathin Oxides: NO Adsorption on Monolayer FeO(111).

Ultrathin metal oxides exhibit unique chemical properties and show promise for applications in heterogeneous catalysis. Monolayer FeO films supported on metal surfaces show large differences in reactivity depending on the metal substrate, potentially enabling tuning of the catalytic properties of these materials. Nitric oxide (NO) adsorption is facile on silver-supported FeO, whereas a similar film grown on platinum is inert to NO under similar conditions. Ab initio calculations link this substrate-dependent behavior to steric hindrance caused by substrate-induced rumpling of the FeO surface, which is stronger for the platinum-supported film. Calculations show that the size of the activation barrier to adsorption caused by the rumpling is dictated by the strength of the metal-oxide interaction, offering a straightforward method for tailoring the adsorption properties of ultrathin films.

Propane σ-Complexes on PdO(101): Spectroscopic Evidence of the Selective Coordination and Activation of Primary C-H Bonds.

Achieving selective C-H bond cleavage is critical for developing catalytic processes that transform small alkanes to value-added products. The present study clarifies the molecular-level origin for an exceptionally strong preference for propane to dissociate on the crystalline PdO(101) surface via primary C-H bond cleavage. Using reflection absorption infrared spectroscopy (RAIRS) and density functional theory (DFT) calculations, we show that adsorbed propane σ-complexes preferentially adopt geometries on PdO(101) in which only primary C-H bonds datively interact with the surface Pd atoms at low propane coverages and are thus activated under typical catalytic reaction conditions. We show that a propane molecule achieves maximum stability on PdO(101) by adopting a bidentate geometry in which a H-Pd dative bond forms at each CH3 group. These results demonstrate that structural registry between the molecule and surface can strongly influence the selectivity of a metal oxide surface in activating alkane C-H bonds.

Disruption of polyubiquitin gene Ubc leads to attenuated resistance against arsenite-induced toxicity in mouse embryonic fibroblasts.

The polyubiquitin gene Ubc is upregulated under oxidative stress induced by arsenite [As(III)]. However, the detailed mechanism of Ubc upregulation and the exact role of ubiquitin (Ub) to protect cells against As(III)-induced toxicity remain unknown. Here, we found that Ubc-/- mouse embryonic fibroblasts (MEFs) exhibited reduced viability under As(III) exposure, although the Nrf2-Keap1 pathway was activated as a cytoprotective response. Intriguingly, due to the reduced polyubiquitination and delayed onset of degradation of Nrf2 in Ubc-/- MEFs, the basal expression levels of Nrf2 target genes were elevated. As(III)-induced accumulation of Ub conjugates occurred in an Nrf2-independent manner, probably due to cellular stress conditions, including reduced proteasomal activity. Increased cellular Ub levels were essential to polyubiquitinate misfolded proteins generated under As(III) exposure and to degrade them by the proteasome. However, when cellular Ub levels decreased, these misfolded proteins were not efficiently polyubiquitinated, but rather accumulated as large protein aggregates inside the cells, causing cytotoxicity. Furthermore, increased activity of the autophagic pathway to clear these aggregates was not observed in Ubc-/- MEFs. Therefore, reduced viability of Ubc-/- MEFs under As(III) exposure may not be due to dysregulation of the Nrf2-Keap1 pathway, but mostly to reduced efficacy to polyubiquitinate and degrade misfolded protein aggregates.

Quantification of neurotransmitters in mouse brain tissue by using liquid chromatography coupled electrospray tandem mass spectrometry.

A simple and rapid liquid chromatography tandem mass spectrometry method has been developed for the determination of BH4, DA, 5-HT, NE, EP, Glu, and GABA in mouse brain using epsilon-acetamidocaproic acid and isotopically labeled neurotransmitters as internal standards. Proteins in the samples were precipitated by adding acetonitrile, and then the supernatants were separated by a Sepax Polar-Imidazole (2.1 mm × 100 mm, i.d., 3 µm) column by adding a mixture of 10 mM ammonium formate in acetonitrile/water (75 : 25, v/v, 300 µl/min) for BH4 and DA. To assay 5-HT, NE, EP, Glu, and GABA; a Luna 3 µ C18 (3.0 mm × 150 mm, i.d., 3 µm) column was used by adding a mixture of 1% formic acid in acetonitrile/water (20 : 80, v/v, 350 µl/min). The total chromatographic run time was 5.5 min. The method was validated for the analysis of samples. The calibration curve was linear between 10 and 2000 ng/g for BH4 (r(2) = 0.995) , 10 and 5000 ng/g for DA (r(2) = 0.997) , 20 and 10000 ng/g for 5-HT (r(2) = 0.994) , NE (r(2) = 0.993) , and EP (r(2) = 0.993) , and 0.2 and 200 µg/g for Glu (r(2) = 0.996) and GABA (r(2) = 0.999) in the mouse brain tissues. As stated above, LC-MS/MS results were obtained and established to be a useful tool for the quantitative analysis of BH4, DA, 5-HT, NE, EP, Glu, and GABA in the experimental rodent brain.

Comparison of international normalized ratio measurement between CoaguChek XS Plus and STA-R coagulation analyzers.

BACKGROUND: Point-of-care testing (POCT) coagulometers are increasingly being used in the hospital setting. We investigated whether the prothrombin time international normalized ratio (INR) results by CoaguChek XS Plus (Roche Diagnostics GmbH, Mannheim, Germany) can be used reliably without being confirmed with the INR results by STA-R system (Diagnostica Stago S.A.S, Asnières sur Seine, France). METHODS: A total of 118 INR measurements by CoaguChek XS Plus and STA-R were compared using Passing/Bablok regression analysis and Bland-Altman plot. Agreement of the INR measurements was further assessed in relation to dosing decision. RESULTS: The correlation of INR measurements between CoaguChek XS Plus and STA-R was excellent (correlation coefficient = 0.964). The mean difference tended to increase as INR results increased and was 0.25 INR in the therapeutic range (2.0-3.0 INR). The overall agreement was fair to good (kappa = 0.679), and 21/118 (17.8%) INR measurements showed a difference in dosing decision. CONCLUSION: The positive bias of CoaguChek XS Plus may be obvious even in the therapeutic INR range, and dosing decision based on the CoaguChek XS Plus INR results would be different from that based on the STA-R results. The INR measurements by POCT coagulometers still need to be confirmed with the laboratory INR measurements.

Evaluation of the efficacy of a pre-pandemic H5N1 vaccine (MG1109) in mouse and ferret models.

The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus causing the next pandemic remains a major concern. In this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1 pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1 A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34 (RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice and ferrets elicited high HI and SN titers in a dose-dependent manner against the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains, (RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient cross-reactivity was not observed against heterosubtypic H9N2 (A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 µg HA/dose of MG1109 were completely protected from lethal challenge with heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 µg HA/dose efficiently suppressed virus growth in the upper respiratory tract and lungs. Vaccinated mice and ferrets also demonstrated attenuation of clinical disease signs and limited virus spread to other organs. Thus, this vaccine provided immunogenic responses in mouse and ferret models even against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the specific strain of HPAI H5N1 virus that would potentially cause the next outbreak is unknown, pre-pandemic vaccine preparation that could provide cross-protection against various H5 strains could be a useful approach in the selection of promising candidate vaccines in the future.

Salt in irrigation water affects the nutritional and visual properties of romaine lettuce (Lactuca sativa L.).

The influence of salinity stress on the growth, appearance, and nutritional compounds, especially phenolic compounds and carotenoids, of romaine lettuce (Lactuca sativa L.), a low salt tolerant plant, was studied. The dry weight, height, and color of the lettuce plants were significantly changed by long-term irrigation (15 days) with higher NaCl concentration (i.e., >100 mM). However, no significant differences were observed in the growth and appearance among the control, all short-term treatments (2 days; 50, 100, 500, and 1000 mM), and long-term irrigation with low salt concentration. Moreover, in romaine lettuce treated with long-term irrigation with 5 mM NaCl, the total carotenoid content increased without color change, and the contents of major carotenoids in romaine lettuce, lutein and beta-carotene, increased 37 and 80%, respectively. No differences were observed in lutein and beta-carotene contents in short-term-treated lettuce. The phenolic content of the romaine lettuce declined with short-term salt irrigation, whereas there were no significant differences among treatments exposed to long-term irrigation. This research indicates that long-term irrigation with relatively low salt concentration, rather than short-term irrigation with high salt concentration, can increase carotenoid content in romaine lettuce without causing a tradeoff in yield or visual quality.

Effect of methyl jasmonate on phenolic compounds and carotenoids of romaine lettuce (Lactuca sativa L.).

The effect of exogenous methyl jasmonate (MeJA) on antioxidative compounds of romaine lettuce ( Lactuca sativa L.) was investigated. Lettuces were treated with various MeJA solutions (0, 0.05, 0.1, 0.25, and 0.5 mM) before harvest. Total phenolic compounds content and antioxidant capacity of romaine lettuce significantly increased after MeJA treatments (0.1, 0.25, and 0.5 mM). The total content of phenolic compounds of the romaine lettuce treated with 0.5 mM MeJA (31.6 microg of gallic acid equivalents/mg of dry weight) was 35% higher than that of the control. The increase in phenolic compound content was attributed to a caffeic acid derivative and an unknown phenolic compound, which also contributed to increased antioxidant capacity. The induction of phenylalanine ammonia-lyase (PAL) activity by the MeJA treatment indicated that phenolic compounds were altered due to the activation of the phenylpropandoid pathway. Total content of carotenoids, including lutein and beta-carotene, of the MeJA-treated lettuce did not change after 8 days of treatment, whereas the content of the control without MeJA decreased after 8 days. This research indicated that preharvest application of MeJA could increase the nutritional value of romaine lettuce under determined conditions discussed in this work.

Effect of methyl jasmonate on phenolics, isothiocyanate, and metabolic enzymes in radish sprout (Raphanus sativus L.).

The effect of spraying exogenous plant hormone methyl jasmonate (MeJA) upon radish sprout (Raphanus sativus L.) was investigated in aspects of total phenolic content (TPC), isothiocyanate content, antioxidant activity of the radish extract, and enzymatic activities of phenylalanine ammonia lyase (PAL) and myrosinase. The MeJA treatment significantly increased the TPC that resulted in the increased DPPH* (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging capacity. In addition, the PAL activity also increased by 60% at 24 h after MeJA treatment. However, the same treatment decreased the amount of 4-methylthio-3-butenylisothiocyanate (MTBITC), a major isothiocyanate in radish sprout and the activity of myrosinase, an enzyme related to produce isothiocyanates.